The invention generally relates to processes for fluorinating compounds in carbon dioxide.
Fluorination, which is generally defined as the contacting of elemental fluorine, or another fluorinating agent, with a substance, is an important industrial process. The choice of fluorinating agent and fluorination conditions often determine the selectivity of the fluorinaton. The fluorinated substance generally undergoes a temporary or permanent change in its physical or chemical properties. Among the changes typically observed in fluorinated substances are bleaching, purification, enhanced lubricity, enhanced impermeability to certain materials, reduction in flammability, and inertness toward chemical reactions such as, for example, resistance to oxidation. The specific changes that are seen, and their magnitude, often depend upon the fluorination conditions as well as on the nature of the substance that is fluorinated. Fluorination can effect changes in the structure of molecules, for example, by replacing certain atoms or groups of atoms such as hydrogen, chlorine, bromine, iodine, carbonyl groups, and hydroxyl groups with fluorine. Fluorine may also be added to sites of unsaturation such as carbon-carbon double bonds. Fluorinating agents that are often used include, but are not limited to, elemental fluorine, xenon difluoride, and functional amines (e.g., N,N-diethyl-1,1,2,3,3,3-hexafluoropropylamine.
Fluorination is typically carried out in solvents or media that are resistant to reaction with fluorinating agents such as halogen-containing solvents like carbon tetrachloride, chlorofluorocarbons, and fluorocarbons. Notwithstanding any potential advantages, these solvents or media may pose potential health and environmental concerns, and should be controlled to minimize possible exposure of personnel and release to the environment. Such environmental concerns could become problematic since selective fluorination processes are being explored for use in pharmaceutical research.
Thus, there is a need in the art for solvents for fluorination and processes using the same that do not have the shortcomings referred to above.
The present invention obviates the need for employing organic solvent reaction media in fluorination processes, particularly processes involving pharmaceutcal compounds. In one aspect, the invention provides a method of fluorinating a substance. The method comprises providing a reaction mixture comprising a liquid or supercritical carbon dioxide reaction medium, a first reactant, and a second reactant, wherein the first reactant is a fluorinating agent. The first reactant and the second reactant are then contacted in the carbon dioxide reaction medium such that the first reactant fluorinates the second reactant.
In another aspect, the invention relates to a reaction mixture. The reaction mixture comprises a first reactant comprising fluorine, a second reactant; and a liquid or supercritical carbon dioxide reaction medium, The first reactant and the second reactant are present in the carbon dioxide reaction medium and the first reactant and the second reactant react such that the second reactant becomes fluorinated.
A further discovery is that carbon dioxide may facilitate the fluorination of solid articles, so that fluorination may be faster and penetrate more deeply than is found when fluorine gas is used alone.
These and other aspects and advantages are provided by the present invention.